Rapid oral desensitization to sirolimus in a patient with lymphangioleiomyomatosis

Sebaaly, Jamielynn; Bowers, Laura W.; Mazur, Joe; Kotloff, Robert M.; Olmsted, Blake R.; Kaplan, Allen P.; Strange, Charlie

doi:10.1016/j.jaip.2015.11.007

Cited by 8 publications

(9 citation statements)

References 12 publications

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“…[5] According to the classification of PEComa of the gastrointestinal tract, benign PEComa had no worrisome features. [18] In contrast, PEComas with uncertain malignant potential exhibited 1 worrisome feature. When 2 or more worrisome features are noted, the diagnosis of malignant PEComa is made.…”

Section: Discussionmentioning

confidence: 99%

“…When 2 or more worrisome features are noted, the diagnosis of malignant PEComa is made. [18] However, an algorithm specific to gynecologic PEComa has been proposed to classify those that are malignant when a minimum of 4 worrisome features are present, and PEComa with fewer than 4 features is classified as benign and/or with uncertain malignant potential. [3]…”

Section: Discussionmentioning

confidence: 99%

“…[14] Sirolimus is an allosteric inhibitor of the mTORC1 receptor, which blocks kinases that regulate growth and cell proliferation. [17,18,21] Gennatas et al described a patient who developed retroperitoneal PEComa with lung metastasis and was treated with an oral mTOR inhibitor. [15] The lung lesions disappeared and the abdominal mass significantly reduced after 12 weeks of treatment, without severe side effects.…”

Section: Discussionmentioning

confidence: 99%

“…[15] Italiano et al reported promising results with the use of mTOR inhibitors in 2 patients with malignant PEComa. [16] Recently, sirolimus was used in the treatment of angiomyolipoma mimicking renal cell carcinoma in a transplanted kidney [17] and LAM in the abdominal cavity, [18] and the results were impressive. The effectiveness of sirolimus against TSC-related AML was also studied in open-label trials.…”

Section: Discussionmentioning

confidence: 99%

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Malignant perivascular epithelioid cell tumor in the female genital tract

Liu

Chao

Lin³

et al. 2019

Medicine

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Background:Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor, located at various anatomic sites, including the female genital tract. This study aimed to evaluate the clinicopathological characteristics of patients with PEComa arising from the female genital tract.Methods:A retrospective study was conducted in Taipei Veterans General Hospital (Taipei VGH) between 2008 and 2018. All published English cases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were also included in the current review.Results:A total of 114 women from PRISMA and 3 women from Taipei VGH were identified. The uterus was the most commonly involved site (82/114, 71.9%), followed by the cervix (12/114, 10.5%). Immunohistochemical staining showed that nearly all gynecological PEComas were positive for human melanoma black 45 (113/114, 99.1%). More than half of the gynecological PEComas were immunoreactive for desmin (50/85, 58.8%). Multi-modality treatment, including surgery and mammalian target of rapamycin (mTOR) inhibitors as targeted therapy, provided long-term disease-free survival (cure rate ranging from 50% to 100%, based on the different anatomic sites of the female genital tract).Conclusion:Multi-modality treatment, including cytoreductive surgery and mTOR inhibitors with/without chemotherapy and/or radiation, should be considered for the management of women with PEComas in the genital tract.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Malignant perivascular epithelioid cell tumor in the female genital tract

Liu

Chao

Lin³

et al. 2019

Medicine

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“…Activation of mTOR, in turn, induces cell growth, motility, and invasion and development of "benign" tumors in LAM and TSC-LAM (14,15). Although many but not all patients with LAM respond, at least initially, to the mTOR inhibitor rapamycin (sirolimus), the dis-ease progresses in others despite treatment (16) thus necessitating lung transplantation (17). Although rapamycin analogs (rapalogs) show beneficial effects, the recurrence of symptoms, a decline in pulmonary function and regrowth of angiolipomas after cessation of treatment, suggests a need for determining novel molecular targets for treatment either alone or as adjuvant therapy with rapalogs (18 -20).…”

mentioning

confidence: 99%

Urokinase-type plasminogen activator (uPA) is critical for progression of tuberous sclerosis complex 2 (TSC2)-deficient tumors

Stepanova

Дергилев

Holman

et al. 2017

Journal of Biological Chemistry

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Lymphangioleiomyomatosis (LAM) is a fatal lung disease associated with germline or somatic inactivating mutations in tuberous sclerosis complex genes ( or ). LAM is characterized by neoplastic growth of smooth muscle-α-actin-positive cells that destroy lung parenchyma and by the formation of benign renal neoplasms called angiolipomas. The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin slows progression of these diseases but is not curative and associated with notable toxicity at clinically effective doses, highlighting the need for better understanding LAM's molecular etiology. We report here that LAM lesions and angiomyolipomas overexpress urokinase-type plasminogen activator (uPA). and mouse embryonic fibroblasts expressed higher uPA levels than their WT counterparts, resulting from the TSC inactivation. Inhibition of uPA expression in -null cells reduced the growth and invasiveness and increased susceptibility to apoptosis. However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC. Induction of glucocorticoid receptor signaling or forkhead box (FOXO) 1/3 inhibition abolished the rapamycin-induced uPA expression in TSC-compromised cells. Moreover, rapamycin-enhanced migration of TSC2-null cells was inhibited by the uPA inhibitor UK122, dexamethasone, and a FOXO inhibitor. uPA-knock-out mice developed fewer and smaller TSC2-null lung tumors, and introduction of uPA shRNA in tumor cells or amiloride-induced uPA inhibition reduced tumorigenesis These findings suggest that interference with the uPA-dependent pathway, when used along with rapamycin, might attenuate LAM progression and potentially other TSC-related disorders.

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Rapid oral desensitization to sirolimus in a patient with lymphangioleiomyomatosis

Cited by 8 publications

References 12 publications

Malignant perivascular epithelioid cell tumor in the female genital tract

Malignant perivascular epithelioid cell tumor in the female genital tract

Urokinase-type plasminogen activator (uPA) is critical for progression of tuberous sclerosis complex 2 (TSC2)-deficient tumors

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